Collagen processing in ras-transfected mouse mammary epithelial cells

A mouse mammary epithelial cell line (NMuMG), after transfection with the c-rasH oncogene, forms invasive tumors in nude mice. NMuMG and NMuMG/p-rasH cells produce similar amounts of collagen (mostly type IV) when grown on plastic. NMuMG cells respond to growth on collagen gels by increasing the rate of collagen synthesis and deposition by 100%, unlike NMuMG/p-rasH cells which synthesize similar amounts of collagen whether grown on plastic or collagen gels. These results suggest that ras transformation partially inhibits the interaction between epithelial cells and the surrounding stroma that is necessary for basement membrane deposition in vivo and consequently may facilitate the invasion of the stroma by transfected cells.     

Diagnostic,prognostic, and therapeutic potency of microRNA 21 in the pathogenesis of colon cancer,current status and prospective

Aberrant microRNA (miR) expression is implicated in multiple human malignancies. miR-21, acting as a proto-oncogene, is involved in a variety of cellular processes and tumorigenesis and is frequently overexpressed in some cancer types. Several tumor suppressors, metastatic, and apoptotic genes have been identified as miR-21 targets, including Ras homolog gene family member B, PTEN, Sprouty2, programmed cell death 4, Integrin-β4, and E-cadherin thereby regulating tumor growth, invasion, and metastasis. There is a growing evidence that miR-21 expression is associated with clinical outcomes in patients with colorectal cancer (CRC). In this review, we summarize the potential diagnostic, prognostic, and therapeutic values of miR-21 in CRC progression for a better understanding and hence a better management of this disease.     

Effect of statin therapy on serum trace element status in dyslipidaemic subjects.

Patients previously not treated with a lipid-lowering agent (n = 20; mean age 49.15 +/- 3.28 years) were treated with either 10 mg/day of Simvastatin (n = 11), or Atorvastatin (n = 9) for 4 months. Fourteen additional patients were recruited from the same clinic at the same hospital as a control group. The medication of these latter patients was unaltered for 4 months and the same parameters were measured as for the statin groups. Serum concentrations of zinc, copper, caeruloplasmin, selenium, glutathione peroxidase (GPx) and C-reactive protein (CRP) were measured together with their lipid profiles pre- and post-treatment. In addition to reducing serum total and low-density lipoprotein (LDL) cholesterol (p < 0.0001), statin treatment was associated with a significant reduction in mean serum zinc (9%, p = 0.03), copper (9%, p < 0.01), caeruloplasmin (24%, p < 0.05), and median CRP (45%, p < 0.03). Similar changes were not observed in the control patients. No significant effects were observed for serum selenium, copper/caeruloplasmin ratio, or GPx (p > 0.05) in either statin or control groups. These changes may be related to the known anti-inflammatory properties of the statin class of drugs.     

Therapeutic potential of RAS prenylation pharmacological inhibitors in the treatment of breast cancer,recent progress,and prospective

Breast cancer is one of the most prevalent malignancies among women around the world. RAS proteins require posttranslational modifications, including protein prenylation for proper membrane localization and signaling. Regulation of RAS signaling via specific and novel pharmacological inhibitors is a potentially novel therapeutic approach in breast cancer therapy. This review summarizes the recent knowledge about the clinical value of RAS prenylation pharmacological inhibitors in breast cancer treatment.     

Role of regulatory miRNAs of the PI3K/AKT/mTOR signaling in the pathogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the common malignant human tumors with high morbidity worldwide. Aberrant activation of the oncogenic phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling is related to clinicopathological features of HCC. Emerging data revealed that microRNAs (miRNAs) have prominent implications for regulating cellular proliferation, differentiation, apoptosis, and metabolism through targeting the PI3K/AKT/mTOR signaling axis. The recognition of the crucial role of miRNAs in hepatocarcinogenesis represents a promising area to identify novel anticancer therapeutics for HCC. The present study summarizes the major findings about the regulatory role of miRNAs in the PI3K/AKT/mTOR pathway in the pathogenesis of HCC.     

Regulation of muscle acetylcholine receptor turnover by β subunit tyrosine phosphorylation

At the neuromuscular junction (NMJ), the postsynaptic localization of muscle acetylcholine receptor (AChR) is regulated by neural signals and occurs via several processes including metabolic stabilization of the receptor. However, the molecular mechanisms that influence receptor stability remain poorly defined. Here, we show that neural agrin and the tyrosine phosphatase inhibitor, pervanadate slow the degradation of surface receptor in cultured muscle cells. Their action is mediated by tyrosine phosphorylation of the AChR β subunit, as agrin and pervandate had no effect on receptor half‐life in AChR‐β^3F/3F muscle cells, which have targeted mutations of the β subunit cytoplasmic tyrosines. Moreover, in wild type AChR‐β^3Y muscle cells, we found a linear relationship between average receptor half‐life and the percentage of AChR with phosphorylated β subunit, with half‐lives of 12.7 and 23 h for nonphosphorylated and phosphorylated receptor, respectively. Surprisingly, pervanadate increased receptor half‐life in AChR‐β^3Y myotubes in the absence of clustering, and agrin failed to increase receptor half‐life in AChR‐β^3F/3F myotubes even in the presence of clustering. The metabolic stabilization of the AChR was mediated specifically by phosphorylation of βY390 as mutation of this residue abolished β subunit phosphorylation but did not affect δ subunit phosphorylation. Receptor stabilization also led to higher receptor levels, as agrin increased surface AChR by 30% in AChR‐β^3Y but not AChR‐β^3F/3F myotubes. Together, these findings identify an unexpected role for agrin‐induced phosphorylation of β^Y390 in downregulating AChR turnover. This likely stabilizes AChR at developing synapses, and contributes to the extended half‐life of AChR at adult NMJs. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 399–410, 2013